The U54 Cooperative Specialized Contraceptive Research Center Grant described in this proposal is comprised of four research and development project and one core laboratory. The long-term, broad objectives of this proposal are to increase the number of contraceptives that are registered for use in family planning programs, to complete the development of new contraceptives with specific advantages over existing methods, and to identify new leads that can be developed into safe and effective methods for men and women. Specifically, a contraceptive vaginal ring that has been designed to deliver norethindrone acetate (NET Ac) and ethynylestradiol (EE) will be tested and registered with the U.S. FDA. Dose-finding studies will be completed with the expectation that the final ring will deliver 1 mg of NET Ac and either 15 or 20 mug of EE for three to four months. This ring will provide better protection against pregnancy by inhibiting ovulation and will provide better bleeding control than contraceptive pills that deliver similar low doses of steroids. The major advantages of this method are that it provides a controlled release system for parenteral steroid delivery that can be controlled by the user herself and does not depend upon medical personnel for insertion and removal. An implant that delivers LHRH analogs is being developed for men. Since this method will suppress both permatogenesis and testosterone production, androgen replacement will be an essential feature of this method. Thus, an implant that will deliver the novel androgen 7alpha-methyl- 19nortestosterone (MENT) for one year is under investigation. It will be used in conjunction with the implant delivering an LHRH agonist. This two- implant system will provide a convenient one-year contraceptive method for men and will provide an additional health-promoting effect on prostate. Finally, contraceptive methods that also prevent sexually transmitted diseases gain increasing importance. Compounds that may protect against HIV and/or chlamydia as well as suppress spermatogenesis will be identified. Appropriate formulations will be designed for animal testing followed by studies in women. This will offer women a method of protecting themselves against sexually transmitted diseases without having to negotiate condom use which is difficult for many women.